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A5288/MULTI-OCTAVE: Management Using Latest Technologies to Optimize Combination Therapy After Viral Failure (MULTI-OCTAVE)

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ClinicalTrials.gov Identifier: NCT01641367
Recruitment Status : Completed
First Posted : July 16, 2012
Results First Posted : February 20, 2018
Last Update Posted : March 15, 2019
Sponsor:
Collaborators:
National Institute of Allergy and Infectious Diseases (NIAID)
AbbVie
Gilead Sciences
Janssen Pharmaceuticals
Merck Sharp & Dohme Corp.
Dimagi Inc.
Information provided by (Responsible Party):
AIDS Clinical Trials Group

Brief Summary:

The study was done to:

  • test a strategy of using a resistance test to choose anti-HIV drugs
  • see how well combinations of new anti-HIV drugs work to lower HIV infection
  • see if taking new anti-HIV drugs together is safe and tolerable
  • see if text messages improve people's anti-HIV drug-taking behavior (only at sites participating in the adherence study)
  • in people taking certain combinations of anti-HIV drugs with an anti-TB drug, compare how these drugs act in the body
  • to see how people do after they stop having frequent clinic visits as part of a research study

Condition or disease Intervention/treatment Phase
HIV-1 Infection Drug: Darunavir Drug: Etravirine Drug: Emtricitabine/tenofovir disoproxil fumarate Drug: Raltegravir Drug: Second line ART regimens - based on a boosted protease inhibitor (bPI) plus two nucleoside analogues (NRTIs) Drug: Study provided drugs according to patient resistance profile (DRV, ETR, RTV, FTC/TDF) + any in country available drug as applicable & available Other: SOC adherence versus SOC+CPI adherence Phase 4

Detailed Description:

A5288 was an open-label phase IV, prospective interventional, strategy study in resource-limited settings (RLS) for HIV-1 infected participants with triple-class experience or resistance to nucleoside reverse transcriptase inhibitors (NRTIs), non-NRTIs (NNRTIs), and protease inhibitors (PIs) and who were failing their current regimen. The use of novel agents and contemporary clinical decision management tools that include standard genotyping and plasma HIV viral load (VL) monitoring were evaluated. The screening genotype results and antiretroviral (ARV) history were used to allocate potential participants to one of four Cohorts (A, B, C or D) and to select an associated ARV regimen based on the Cohort assignment. In brief, individuals assigned to Cohort A continued on the same PI as in their second-line regimen, with the ability to modify NRTIs. Those assigned to Cohort B who were negative for hepatitis B were randomized to receive RAL and DRV/RTV with either the best available NRTIs (Cohort B1) or ETR (Cohort B2). If they were positive for hepatitis B they were assigned to Cohort B3 and received RAL, DRV/RTV and either FTC/TDF or 3TC/TDF. Individuals assigned to Cohort C received RAL and DRV/RTV with the best available NRTIs. Those ineligible for Cohorts A, B or C were assigned to Cohort D and received the best available regimen that included study provided drugs and any locally provided drugs.

At sites where feasible and relevant, the study evaluated an adherence support intervention. This involved a randomized comparison of a cell phone-based adherence support intervention plus local standard-of-care adherence support procedures (CPI+SOC) versus the SOC adherence support procedures.

Participants enrolled to the study in Step 1. If a participant experienced a confirmed virologic failure (defined as two consecutive HIV-1 RNA measures >= 1000 copies/mL) at/after 22 weeks on their Step 1 regimen, they had another genotype test performed and cohort/regimen selected for Step 2. With the exception of one additional visit 4 weeks after enrollment to Step 2, the visit schedule for Step 2 followed the participant's original Step 1 schedule throughout the remainder of follow up.

Participants were followed in Steps 1 and 2 until 48 weeks after the last participant was enrolled to Step 1. During the first 48 weeks after Step 1 enrollment, clinic visits occurred at weeks 4, 12, 24, 36 and 48. After week 48, visits occurred every 12 weeks for adherence, safety and efficacy measures.

Participants had a final step 1/2 visit between November 22, 2016 and February 13, 2017. At the final step 1/2 visit, participants taking RAL, ETR, or DRV who were unable to obtain these drugs locally (e.g., through local treatment programs), and were otherwise eligible, entered Step 3 and continued to receive these drugs through the study for up to 96 additional weeks. Step 3 participants were dispensed ARVs every 12 weeks and had clinical assessments every 24 weeks. The purpose of Step 3 was to assist participants with the transition back to local care.

The primary analysis specified in the protocol and in the Statistical Analysis Plan was to estimate the proportion of participants in the overall study population who were virologically suppressed (HIV-1 RNA ≤200 copies/mL) at week 48 with a 95% confidence interval.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 545 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Management Using the Latest Technologies in Resource-limited Settings to Optimize Combination Therapy After Viral Failure (MULTI-OCTAVE)
Actual Study Start Date : February 22, 2013
Actual Primary Completion Date : November 23, 2016
Actual Study Completion Date : December 31, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: Cohort A

Under Protocol version 1.0:

No resistance to NRTIs, PIs, or NNRTI

• Continue current second-line regimen; NRTIs could be modified

Changed under LOA#2 to:

No LPV/RTV resistance and susceptible to at least one NRTI, regardless of NNRTI resistance or prior RAL exposure

• Continue second-line regimen which may include LPV/RTV; NRTIs could be modified

Changed under LOA#3 to:

No LPV/RTV resistance and susceptible to at least one NRTI, regardless of NNRTI resistance or prior RAL exposure

• Continue PI backbone; NRTIs could be modified. If on a RAL-containing regimen, RAL must be discontinued.

Drug: Second line ART regimens - based on a boosted protease inhibitor (bPI) plus two nucleoside analogues (NRTIs)
LPV/r and ATV/r were the preferred bPIs for second-line ART. TDF + (3TC or FTC) or AZT + 3TC were the most frequent NRTI backbones. Cohort A did not include any of the new drugs; therefore, it is distinct from Cohorts B, C, and D.

Other: SOC adherence versus SOC+CPI adherence
  • not participating in the adherence randomization; OR
  • randomized to SOC adherence; OR
  • randomized to SOC+CPI adherence.

Experimental: Sub-cohort B1

Under Protocol version 1.0:

Susceptible to DRV/RTV and ETR with or without resistance to NRTIs (and may have resistance to other PIs) and without active hepatitis B infection at screening

• Best available NRTIs, RAL, & DRV/RTV

Changed under LOA#2 to:

Resistance to LPV/RTV but susceptible to DRV/RTV and ETR and with no prior RAL exposure and regardless of NRTI resistance (and without active hepatitis B infection at screening) OR Resistance to all NRTIs (i.e. susceptible to none) but susceptible to DRV/RTV and ETR and with no prior RAL exposure (and without active hepatitis B infection at screening)

• Best available NRTIs, RAL, & DRV/RTV

Drug: Darunavir
Participants were administered darunavir orally as one 600 mg tablet twice a day (1200 mg per day) with food (taken with Ritonavir 100 mg twice a day [200 mg per day])
Other Names:
  • DRV
  • Prezista

Drug: Raltegravir
Participants were administered Raltegravir orally as one 400 mg tablet twice daily (800 mg per day), with or without food
Other Names:
  • RAL
  • Isentress

Other: SOC adherence versus SOC+CPI adherence
  • not participating in the adherence randomization; OR
  • randomized to SOC adherence; OR
  • randomized to SOC+CPI adherence.

Experimental: Sub-cohort B2

Under Protocol version 1.0:

Susceptible to DRV/RTV and ETR with or without resistance to NRTIs (and may have resistance to other PIs) and without active hepatitis B infection at screening

• ETR, RAL, and DRV/RTV

Changed under LOA#2 to:

Resistance to LPV/RTV but susceptible to DRV/RTV and ETR and with no prior RAL exposure and regardless of NRTI resistance (and without active hepatitis B infection at screening) OR Resistance to all NRTIs (i.e. susceptible to none) but susceptible to DRV/RTV and ETR and with no prior RAL exposure (and without active hepatitis B infection at screening)

• ETR, RAL, and DRV/RTV

Drug: Darunavir
Participants were administered darunavir orally as one 600 mg tablet twice a day (1200 mg per day) with food (taken with Ritonavir 100 mg twice a day [200 mg per day])
Other Names:
  • DRV
  • Prezista

Drug: Etravirine
Patients were administered Etravirine orally as two 100 mg tablets or one 200 mg tablet twice a day (400 mg per day) following a meal.
Other Names:
  • ETR
  • Intelence

Drug: Raltegravir
Participants were administered Raltegravir orally as one 400 mg tablet twice daily (800 mg per day), with or without food
Other Names:
  • RAL
  • Isentress

Other: SOC adherence versus SOC+CPI adherence
  • not participating in the adherence randomization; OR
  • randomized to SOC adherence; OR
  • randomized to SOC+CPI adherence.

Experimental: Sub-cohort B3

Under Protocol version 1.0:

Susceptible to DRV/RTV and ETR with or without resistance to NRTIs (and may have resistance to other PIs) and with active hepatitis B infection at screening

• RAL, DRV/RTV, and FTC/TDF or TDF+3TC

Changed under LOA#2 to:

Resistance to LPV/RTV but susceptible to DRV/RTV and ETR and with no prior RAL exposure and regardless of NRTI resistance (with active hepatitis B infection at screening) OR Resistance to all NRTIs (i.e. susceptible to none) but susceptible to DRV/RTV and ETR and with no prior RAL exposure (with active hepatitis B infection at screening)

• RAL, DRV/RTV, and FTC/TDF or TDF+3TC

Drug: Darunavir
Participants were administered darunavir orally as one 600 mg tablet twice a day (1200 mg per day) with food (taken with Ritonavir 100 mg twice a day [200 mg per day])
Other Names:
  • DRV
  • Prezista

Drug: Emtricitabine/tenofovir disoproxil fumarate
Patients were administered FTC/TDF orally as one fixed dose combination tablet (FTC 200 mg/TDF 300 mg) once daily, with or without food.
Other Names:
  • FTC/TDF
  • Truvada

Drug: Raltegravir
Participants were administered Raltegravir orally as one 400 mg tablet twice daily (800 mg per day), with or without food
Other Names:
  • RAL
  • Isentress

Other: SOC adherence versus SOC+CPI adherence
  • not participating in the adherence randomization; OR
  • randomized to SOC adherence; OR
  • randomized to SOC+CPI adherence.

Experimental: Cohort C

Under Protocol version 1.0:

Resistance to NRTIs and ETR or resistance to ETR alone (and may have resistance to PIs other than DRV)

• Best available NRTIs, RAL, and DRV/RTV

Changed under LOA#2:

Resistance to LPV/RTV and ETR but susceptible to DRV/RTV and with no prior RAL exposure and regardless of NRTI resistance OR Resistance to ETR and to all NRTIs (i.e. susceptible to none) but susceptible to DRV/RTV and with no prior RAL exposure

• Best available NRTIs, RAL, and DRV/RTV

Drug: Darunavir
Participants were administered darunavir orally as one 600 mg tablet twice a day (1200 mg per day) with food (taken with Ritonavir 100 mg twice a day [200 mg per day])
Other Names:
  • DRV
  • Prezista

Drug: Raltegravir
Participants were administered Raltegravir orally as one 400 mg tablet twice daily (800 mg per day), with or without food
Other Names:
  • RAL
  • Isentress

Other: SOC adherence versus SOC+CPI adherence
  • not participating in the adherence randomization; OR
  • randomized to SOC adherence; OR
  • randomized to SOC+CPI adherence.

Experimental: Cohort D

Under Protocol version 1.0:

Multiple NRTI resistance and/or DRV/RTV resistance or prior RAL exposure:

• Best available regimen, including study-provided and any locally available drugs

Changed under LOA#2:

Not eligible for Cohort A, B, or C:

• Best available regimen, including study-provided and any locally available drugs

Updated under protocol v2.0:

• Best available ART regimen, including study-provided and any locally available non-experimental drugs

Drug: Study provided drugs according to patient resistance profile (DRV, ETR, RTV, FTC/TDF) + any in country available drug as applicable & available
For Cohort D, in many situations a participant received the same regimen that patients are getting in Cohorts B and C if that was the best combination that can be obtained according to his/her resistance profile and drug availability (as for many countries there were no further drug options beyond the available study drugs).

Other: SOC adherence versus SOC+CPI adherence
  • not participating in the adherence randomization; OR
  • randomized to SOC adherence; OR
  • randomized to SOC+CPI adherence.




Primary Outcome Measures :
  1. Proportion of Participants With Plasma HIV-1 RNA ≤200 Copies/mL at 48 Weeks [ Time Frame: 48 weeks after the date of entry ]

    The measurement closest to exactly 48 weeks (ie, 7x48=336 days) after the date of entry, within the window of 48 weeks ± 6 weeks (specifically 295 to 378 days after randomization, inclusive).

    The analysis in the protocol and in the Stat. Analysis Plan involved estimating the proportion of participants in the overall study population with HIV-1 RNA ≤200 copies/mL at week 48 with a 95% confidence interval calculated via a Wald approach. Death or lost to follow-up before week 48 was considered as HIV-1 RNA>200 copies/mL at week 48. Missing results at week 48 were considered as HIV-1 RNA >200 copies/mL at week 48 unless the immediately preceding and succeeding HIV-1 RNA measurements were ≤200 copies/mL. Since the primary analysis was on the total study population, overall results were also submitted. All participants in B3 had HIV-1 RNA ≤200 copies/mL at week 48. Therefore, Wald confidence interval could not be computed for B3 and Clopper-Pearson Exact confidence interval is provided.



Secondary Outcome Measures :
  1. Proportion of Participants With Plasma HIV-1 RNA ≤200 Copies/mL at 24 Weeks [ Time Frame: 24 weeks after the date of entry ]

    The measurement closest to exactly 24 weeks (ie, 7x24=168 days) after the date of entry, within the window of 24 weeks ± 6 weeks (specifically 127 to 210 days after randomization, inclusive).

    The analysis in the protocol and in the Stat. Analysis Plan involved estimating the proportion of participants in the overall study population with HIV-1 RNA ≤200 copies/mL at week 24 with a 95% confidence interval calculated via a Wald approach. Death or lost to follow-up before week 24 was considered as HIV-1 RNA>200 copies/mL at week 24. Missing results at week 24 were considered as HIV-1 RNA >200 copies/mL at week 24 unless the immediately preceding and succeeding HIV-1 RNA measurements were ≤200 copies/mL. Since the primary analysis was on the total study population, overall results were also submitted. All participants in B3 had HIV-1 RNA ≤200 copies/mL at week 24. Therefore, Wald confidence interval could not be computed for B3 and Clopper-Pearson Exact confidence interval is provided.


  2. Proportion of Participants With Plasma HIV-1 RNA ≤200 Copies/mL at 72 Weeks [ Time Frame: 72 weeks after the date of entry ]

    The measurement closest to exactly 72 weeks (ie, 7x72=504 days) after the date of entry, within the window of 72 weeks ± 6 weeks (specifically 463 to 546 days, inclusive).

    The analysis in the protocol and in the Analysis Plan involved estimating the proportion of participants in the overall study population with HIV-1 RNA ≤200 copies/mL at week 72 with a 95% confidence interval calculated via a Wald approach. Death or lost to follow-up before week 72 was considered as HIV-1 RNA>200 copies/mL at week 72. If a result was expected, missing results at week 72 were considered as HIV-1 RNA >200 copies/mL at week 72 unless the immediately preceding and succeeding HIV-1 RNA measurements were ≤200 copies/mL. Since the primary analysis was on the total study population, overall results were also submitted. All participants in B3 had HIV-1 RNA ≤200 copies/mL at week 72. Therefore, Wald confidence interval could not be computed for B3 and Clopper-Pearson Exact confidence interval is provided.


  3. Number of Weeks of Follow-up [ Time Frame: From study entry through Step 1/2 follow-up ]
    All participants were followed on step 1/2 until 48 weeks after the last participant was enrolled to step 1 regardless of virologic status or treatment switches. Length of follow-up varied by Cohort.

  4. Time to Confirmed Virologic Failure, Defined as First HIV-1 RNA ≥1000 Copies/mL at or After 24 Weeks on Study [ Time Frame: From week 24 through Step 1/2 follow-up; median (IQR) step 1/2 follow-up was 72 (72,108) weeks ]
    Virologic failure was confirmed by the next HIV-1 RNA measurement ≥1000 copies/mL (irrespective of time between initial and confirmatory measure [specimens on separate dates] and treatment status). A week 24 measurement included HIV-1 RNA obtained ≥7*22=154 days after study entry (to allow for 14 day window for scheduling the visit). HIV-1 RNA measurements through and including 21 November 2016 were considered in identifying an initial failing measurement, allowing HIV-1 RNA at the close-out visit between 22 November 2016 and 13 February 2017 to be a confirmatory measure. Event times were the scheduled week of the initial failing measurement (RNA scheduled at week 0, 12, 24, 48 and every 24 weeks after). Censoring times were the scheduled week of the last RNA result. Length of follow-up varied by Cohort.

  5. Number of Participants With Confirmed Virologic Failure, Defined as First HIV-1 RNA ≥1000 Copies/mL at or After 24 Weeks on Study [ Time Frame: From week 24 through Step 1/2 follow-up; median (IQR) step 1/2 follow-up was 72 (72,108) weeks ]
    Virologic failure was confirmed by the next HIV-1 RNA measurement ≥1000 copies/mL (irrespective of time between initial and confirmatory measure [specimens on separate dates] and treatment status). A week 24 measurement included HIV-1 RNA obtained ≥7*22=154 days after study entry (to allow for 14 day window for scheduling the visit). HIV-1 RNA measurements through and including 21 November 2016 were considered in identifying an initial failing measurement, allowing HIV-1 RNA at the close-out visit between 22 November 2016 and 13 February 2017 to be a confirmatory measure. Length of follow-up varied by Cohort.

  6. Percent of Participants With Confirmed Virologic Failure by Week 48 [ Time Frame: From week 24 to Week 48 ]
    Results report percent of participants reaching outcome by week 48 using Kaplan-Meier method. Virologic failure was confirmed by the next HIV-1 RNA measurement ≥1000 copies/mL (irrespective of time between initial and confirmatory measure [specimens on separate dates] and treatment status). A week 24 measurement included HIV-1 RNA obtained ≥7*22=154 days after study entry(to allow for 14 day window for scheduling the visit). HIV-1 RNA measurements through and including 21 November 2016 were considered in identifying an initial failing measurement,allowing HIV-1 RNA at the close-out visit between 22 November 2016 and 13 February 2017 to be a confirmatory measure. Event times were the scheduled week of the initial failing measurement (RNA scheduled at week 0, 12, 24, 48 and every 24 weeks after). Censoring times were the scheduled week of the last RNA result. Length of follow-up varied by Cohort.

  7. Time to Confirmed Virologic Failure, Defined as First HIV-1 RNA ≥1000 Copies/mL at or After 24 Weeks on Study, With a New Resistance-associated Mutation Detected in Population-based Sequencing [ Time Frame: From week 24 through Step 1/2 follow-up; median (IQR) step 1/2 follow-up was 72 (72,108) weeks ]
    Virologic failure was confirmed by the next HIV-1 RNA measurement ≥1000 copies/mL (irrespective of time between initial and confirmatory measure [specimens on separate dates] and treatment status). A week 24 measurement included HIV-1 RNA obtained ≥7*22=154 days after study entry (to allow for 14 day window for scheduling the visit). HIV-1 RNA measurements through and including 21 November 2016 were considered in identifying an initial failing measurement, allowing HIV-1 RNA at the close-out visit between 22 November 2016 and 13 February 2017 to be a confirmatory measure. Event times were the scheduled week of the initial failing measurement (RNA scheduled at week 0, 12, 24, 48 and every 24 weeks after). Censoring times were the scheduled week of the last RNA result. Length of follow-up varied by Cohort. A new resistance-associated mutation is defined as one not present in the genotype prior to entry.

  8. Number of Participants With Confirmed Virologic Failure, Defined as First HIV-1 RNA ≥1000 Copies/mL at or After 24 Weeks on Study, With a New Resistance-associated Mutation Detected in Population-based Sequencing [ Time Frame: From week 24 through Step 1/2 follow-up; median (IQR) step 1/2 follow-up was 72 (72,108) weeks ]
    Virologic failure was confirmed by the next HIV-1 RNA measurement ≥1000 copies/mL (irrespective of time between initial and confirmatory measure[specimens on separate dates] and treatment status). A week 24 measurement included HIV-1 RNA obtained ≥7*22=154 days after study entry (to allow for 14 day window for scheduling the visit).HIV-1 RNA measurements through and including 21 November 2016 were considered in identifying an initial failing measurement, allowing HIV-1 RNA at the close-out visit between 22 November 2016 and 13 February 2017 to be a confirmatory measure. Length of follow-up varied by Cohort. A new resistance-associated mutation is defined as one not present in the genotype prior to entry.

  9. Percent of Participants With Confirmed Virologic Failure, Defined as First HIV-1 RNA ≥1000 Copies/mL at or After 24 Weeks on Study, With a New Resistance-associated Mutation Detected in Population-based Sequencing, by Week 48 [ Time Frame: From week 24 to Week 48 ]
    Results report percent of participants reaching outcome by week 48 using Kaplan-Meier method. Virologic failure was confirmed by the next HIV-1 RNA measurement ≥1000 copies/mL (irrespective of time between initial and confirmatory measure[specimens on separate dates] and treatment status). A week 24 measurement included HIV-1 RNA obtained ≥7*22=154 days after study entry(to allow for 14 day window for scheduling the visit).HIV-1 RNA measurements through and including 21 November 2016 were considered in identifying an initial failing measurement,allowing HIV-1 RNA at the close-out visit between 22 November 2016 and 13 February 2017 to be a confirmatory measure.Event times were the scheduled week of the initial failing measurement(RNA scheduled at week 0, 12, 24, 48 and every 24 weeks after).Censoring times were the scheduled week of the last RNA result.Length of follow-up varied by Cohort.A new resistance-associated mutation is defined as one not present in the genotype prior to entry.

  10. Time From Study Entry/Randomization to Death [ Time Frame: From study entry through Step 1/2 follow-up; median (IQR) step 1/2 follow-up was 72 (72,108) weeks ]
    Event time was the exact week of death. Censoring time was the earlier of last contact week and the week of the last step 1/2 visit. Length of follow-up varied by Cohort.

  11. Percent of Participants Experiencing Death by Week 48 [ Time Frame: From study entry to Week 48 ]
    Results report percent of participants reaching outcome by week 48 using Kaplan-Meier method. Event time was the exact week of death. Censoring time was the earlier of last contact week and the week of the last step 1/2 visit.

  12. Time From Study Entry/Randomization to the First of Death, an AIDS-defining Event or a Non-AIDS-defining Event [ Time Frame: From study entry through Step 1/2 follow-up; median (IQR) step 1/2 follow-up was 72 (72,108) weeks ]
    Event time was the exact week of death, AIDS-defining event or non-AIDS defining event. Censoring time was the earlier of last contact week and the week of the last step 1/2 visit. Only new events were considered, an event that was also reported at or prior to study entry was not included. If a participant experienced multiple events, then the time of the first event was used in the analysis. AIDS defining events included parasitic, fungal, bacterial, and viral infections as well as neoplastic diseases, and neurological disorders. Non-AIDS defining events included malignancies, diabetes, neuropathies, cardiac and renal events. Length of follow-up varied by Cohort.

  13. Percent of Participants Experiencing Death, AIDS-defining Event or a Non-AIDS-defining Event by Week 48 [ Time Frame: From study entry to Week 48 ]
    Results report percent of participants reaching outcome by week 48 using Kaplan-Meier method. Event time was the exact week of death, AIDS-defining event or non-AIDS defining event. Censoring time was the earlier of last contact week and the week of the last step 1/2 visit. Only new events were considered, an event that was also reported at or prior to study entry was not included. If a participant experienced multiple events, then the time of the first event was used in the analysis. AIDS defining events included parasitic, fungal, bacterial, and viral infections as well as neoplastic diseases, and neurological disorders. Non-AIDS defining events included malignancies, diabetes, neuropathies, cardiac and renal events.

  14. Time From Study Entry/Randomization to the First of Death or Hospitalization. [ Time Frame: From study entry through Step 1/2 follow-up; median (IQR) step 1/2 follow-up was 72 (72,108) weeks ]
    Event time was the exact week of death or hospitalization. Censoring time was the earlier of last contact week and the week of the last step 1/2 visit. If a participant experienced multiple events, then the time of the first event was used in the analysis. Length of follow-up varied by Cohort.

  15. Percent of Participants With Death or Hospitalization by Week 48 [ Time Frame: From study entry to Week 48 ]
    Results report percent of participants reaching outcome by week 48 using Kaplan-Meier method. Event time was the exact week of death or hospitalization. Censoring time was the earlier of last contact week and the week of the last step 1/2 visit. If a participant experienced multiple events, then the time of the first event was used in the analysis.

  16. Time From Study Entry/Randomization to Treatment Modification or Discontinuation. [ Time Frame: From study entry through Step 1/2 follow-up; median (IQR) step 1/2 follow-up was 72 (72,108) weeks ]
    Treatment modification is defined as the first occurrence of a substitution or subtraction of one or more drugs in the study regimen, a temporary hold lasting 7 days or longer, or the addition of a new drug to the regimen. This would not include splitting any fixed dose combination medications if the participant continues on the active drugs of the combination. Event time was the exact week of the modification or discontinuation. Censoring time was the earlier of last contact week and the week of the last step 1/2 visit. Length of follow-up varied by Cohort.

  17. Percent of Participants With Treatment Modification or Discontinuation by Week 48 [ Time Frame: From study entry to Week 48 ]
    Results report percent of participants reaching outcome by week 48 using Kaplan-Meier method. Treatment modification is defined as the first occurrence of a substitution or subtraction of one or more drugs in the study regimen, a temporary hold lasting 7 days or longer, or the addition of a new drug to the regimen. This would not include splitting any fixed dose combination medications if the participant continues on the active drugs of the combination. Event time was the exact week of the modification or discontinuation. Censoring time was the earliest time point between last dose week and the week of the last step 1/2 visit.

  18. Time From Study Entry/Randomization to Treatment Modification or Discontinuation Due to Toxicity [ Time Frame: From study entry through Step 1/2 follow-up; median (IQR) step 1/2 follow-up was 72 (72,108) weeks ]
    Treatment modification is defined as the first occurrence of a substitution or subtraction of one or more drugs in the study regimen, a temporary hold lasting 7 days or longer, or the addition of a new drug to the regimen, due to an adverse event. This would not include splitting any fixed dose combination medications if the participant continues on the active drugs of the combination. Event time was the exact week of the modification or discontinuation. Censoring time was the earliest time point between last dose week and the week of the last step 1/2 visit. Length of follow-up varied by Cohort. DAIDS AE Grading Table, Version 1.0 was used.

  19. Percent of Participants With Treatment Modification or Discontinuation Due to Toxicity by Week 48 [ Time Frame: From study entry to Week 48 ]
    Results report percent of participants reaching outcome by week 48 using Kaplan-Meier method. Treatment modification is defined as the first occurrence of a substitution or subtraction of one or more drugs in the study regimen, a temporary hold lasting 7 days or longer, or the addition of a new drug to the regimen, due to an adverse event. This would not include splitting any fixed dose combination medications if the participant continues on the active drugs of the combination. Event time was the exact week of the modification or discontinuation. Censoring time was the earliest time point between last dose week and the week of the last step 1/2 visit. DAIDS AE Grading Table, Version 1.0 was used.

  20. Time From Study Entry/Randomization to the Development of Immune Reconstitution Inflammatory Syndrome (IRIS) [ Time Frame: From study entry through Step 1/2 follow-up; median (IQR) step 1/2 follow-up was 72 (72,108) weeks ]
    Event time was the exact week of the diagnosis. Censoring time was the earlier of last contact week and the week of the last step 1/2 visit. Length of follow-up varied by Cohort.

  21. Percent of Participants That Developed Immune Reconstitution Inflammatory Syndrome (IRIS) by Week 48 [ Time Frame: From study entry to week 48 ]
    Results report percent of participants reaching outcome by week 48 using Kaplan-Meier method. Event time was the exact week of the diagnosis. Censoring time was the earlier of last contact week and the week of the last step 1/2 visit.

  22. Time to First Dose Modification Due to Grade 3 or 4 Toxicity [ Time Frame: From study entry through Step 1/2 follow-up; median (IQR) step 1/2 follow-up was 72 (72,108) weeks ]
    Event time was the exact week of the modification. Censoring time was the earliest time point between last dose week and the week of the last step 1/2 visit. Length of follow-up varied by Cohort. DAIDS AE Grading Table, Version 1.0 was used.

  23. Percent of Participants With a Dose Modification Due to Grade 3 or 4 Toxicity by Week 48 [ Time Frame: From study entry to week 48 ]
    Results report percent of participants reaching outcome by week 48 using Kaplan-Meier method. Event time was the exact week of the modification. Censoring time was the earliest time point between last dose week and the week of the last step 1/2 visit. DAIDS AE Grading Table, Version 1.0 was used.

  24. Change From Baseline in CD4+ T-cell Count [ Time Frame: Baseline, week 24, 48, and 72 ]
    Baseline is defined as the last measurement obtained on or before the earlier of the following two dates: the date of entry/randomization plus three days (this is the time allowed in the protocol for starting study-defined ART) and the date of starting the study-defined ARV regimen (this second date applies only to Cohorts B, C and D as there is no change of regimen for patients in Cohort A)

  25. Change From Baseline in Fasting Values of Total Cholesterol [ Time Frame: Baseline, week 24, 48 and 72 ]
    Baseline is defined as the last measurement obtained on or before the earlier of the following two dates: the date of entry/randomization plus three days (this is the time allowed in the protocol for starting study-defined ART) and the date of starting the study-defined ARV regimen (this second date applies only to Cohorts B, C and D as there is no change of regimen for patients in Cohort A)

  26. Change From Baseline in Fasting Values of High-density Lipoprotein Cholesterol [ Time Frame: Baseline, week 24, 48 and 72 ]
    Baseline is defined as the last measurement obtained on or before the earlier of the following two dates: the date of entry/randomization plus three days (this is the time allowed in the protocol for starting study-defined ART) and the date of starting the study-defined ARV regimen (this second date applies only to Cohorts B, C and D as there is no change of regimen for patients in Cohort A)]

  27. Change From Baseline in Fasting Values of Calculated Low-density Lipoprotein Cholesterol [ Time Frame: Baseline, week 24, 48 and 72 ]
    Baseline is defined as the last measurement obtained on or before the earlier of the following two dates: the date of entry/randomization plus three days (this is the time allowed in the protocol for starting study-defined ART) and the date of starting the study-defined ARV regimen (this second date applies only to Cohorts B, C and D as there is no change of regimen for patients in Cohort A)

  28. Change From Baseline in Fasting Values of Triglycerides [ Time Frame: Baseline, week 24, 48 and 72 ]
    Baseline is defined as the last measurement obtained on or before the earlier of the following two dates: the date of entry/randomization plus three days (this is the time allowed in the protocol for starting study-defined ART) and the date of starting the study-defined ARV regimen (this second date applies only to Cohorts B, C and D as there is no change of regimen for patients in Cohort A)

  29. Change From Baseline in Fasting Values of Glucose [ Time Frame: Baseline, week 24, 48 and 72 ]
    Baseline is defined as the last measurement obtained on or before the earlier of the following two dates: the date of entry/randomization plus three days (this is the time allowed in the protocol for starting study-defined ART) and the date of starting the study-defined ARV regimen (this second date applies only to Cohorts B, C and D as there is no change of regimen for patients in Cohort A)

  30. Proportion of Participants With Plasma HIV-1 RNA ≤200 Copies/mL at 48 Weeks [CPI+SOC v SOC] [ Time Frame: 48 weeks after the date of entry ]

    The measurement closest to exactly 48 weeks (ie, 7x48=336 days) after the date of entry, within the window of 48 weeks ± 6 weeks (specifically 295 to 378 days after randomization, inclusive).

    The analysis in the protocol and in the Stat. Analysis Plan involved estimating the proportion of participants in the overall study population with HIV-1 RNA ≤200 copies/mL at week 48 with a 95% confidence interval calculated via a Wald approach. Death or lost to follow-up before week 48 was considered as HIV-1 RNA>200 copies/mL at week 48. Missing results at week 48 were considered as HIV-1 RNA >200 copies/mL at week 48 unless the immediately preceding and succeeding HIV-1 RNA measurements were ≤200 copies/mL.


  31. Proportion of Participants With Plasma HIV-1 RNA ≤200 Copies/mL at 24 Weeks [CPI+SOC v SOC] [ Time Frame: 24 weeks after the date of entry ]

    The measurement closest to exactly 24 weeks (ie, 7x24=168 days) after the date of entry, within the window of 24 weeks ± 6 weeks (specifically 127 to 210 days after randomization, inclusive).

    The analysis in the protocol and in the Stat. Analysis Plan involved estimating the proportion of participants in the overall study population with HIV-1 RNA ≤200 copies/mL at week 24 with a 95% confidence interval calculated via a Wald approach. Death or lost to follow-up before week 24 was considered as HIV-1 RNA>200 copies/mL at week 24. Missing results at week 24 were considered as HIV-1 RNA >200 copies/mL at week 24 unless the immediately preceding and succeeding HIV-1 RNA measurements were ≤200 copies/mL.


  32. Proportion of Participants With Plasma HIV-1 RNA ≤200 Copies/mL at 72 Weeks [CPI+SOC v SOC] [ Time Frame: 72 weeks after the date of entry ]

    The measurement closest to exactly 72 weeks (ie, 7x72=504 days) after the date of entry, within the window of 72 weeks ± 6 weeks (specifically 463 to 546 days, inclusive).

    The analysis in the protocol and in the Analysis Plan involved estimating the proportion of participants in the overall study population with HIV-1 RNA ≤200 copies/mL at week 72 with a 95% confidence interval calculated via a Wald approach. Death or lost to follow-up before week 72 was considered as HIV-1 RNA>200 copies/mL at week 72. If a result was expected, missing results at week 72 were considered as HIV-1 RNA >200 copies/mL at week 72 unless the immediately preceding and succeeding HIV-1 RNA measurements were ≤200 copies/mL.


  33. Number of Weeks of Follow-up [CPI+SOC v SOC] [ Time Frame: From study entry through Step 1/2 follow-up ]
    All participants were followed on step 1/2 until 48 weeks after the last participant was enrolled to step 1 regardless of virologic status or treatment switches.

  34. Time to Confirmed Virologic Failure, Defined as First HIV-1 RNA ≥1000 Copies/mL at or After 24 Weeks on Study [CPI+SOC v SOC] [ Time Frame: From week 24 through Step 1/2 follow-up; median (IQR) step 1/2 follow-up was 72 (72,108) weeks ]
    Virologic failure was confirmed by the next HIV-1 RNA measurement ≥1000 copies/mL (irrespective of time between initial and confirmatory measure [specimens on separate dates] and treatment status). A week 24 measurement included HIV-1 RNA obtained ≥7*22=154 days after study entry (to allow for 14 day window for scheduling the visit). HIV-1 RNA measurements through and including 21 November 2016 were considered in identifying an initial failing measurement, allowing HIV-1 RNA at the close-out visit between 22 November 2016 and 13 February 2017 to be a confirmatory measure. Event times were the scheduled week of the initial failing measurement (RNA scheduled at week 0, 12, 24, 48 and every 24 weeks after). Censoring times were the scheduled week of the last RNA result.

  35. Number of Participants With Confirmed Virologic Failure, Defined as First HIV-1 RNA ≥1000 Copies/mL at or After 24 Weeks on Study [CPI+SOC v SOC] [ Time Frame: From week 24 through Step 1/2 follow-up; median (IQR) step 1/2 follow-up was 72 (72,108) weeks ]
    Virologic failure was confirmed by the next HIV-1 RNA measurement ≥1000 copies/mL (irrespective of time between initial and confirmatory measure [specimens on separate dates] and treatment status). A week 24 measurement included HIV-1 RNA obtained ≥7*22=154 days after study entry (to allow for 14 day window for scheduling the visit). HIV-1 RNA measurements through and including 21 November 2016 were considered in identifying an initial failing measurement, allowing HIV-1 RNA at the close-out visit between 22 November 2016 and 13 February 2017 to be a confirmatory measure.

  36. Percent of Participants With Confirmed Virologic Failure by Week 48 [CPI+SOC v SOC] [ Time Frame: From week 24 to Week 48 ]
    Results report percent of participants reaching outcome by week 48 using Kaplan-Meier method. Virologic failure was confirmed by the next HIV-1 RNA measurement ≥1000 copies/mL (irrespective of time between initial and confirmatory measure [specimens on separate dates] and treatment status). A week 24 measurement included HIV-1 RNA obtained ≥7*22=154 days after study entry(to allow for 14 day window for scheduling the visit). HIV-1 RNA measurements through and including 21 November 2016 were considered in identifying an initial failing measurement,allowing HIV-1 RNA at the close-out visit between 22 November 2016 and 13 February 2017 to be a confirmatory measure. Event times were the scheduled week of the initial failing measurement (RNA scheduled at week 0, 12, 24, 48 and every 24 weeks after). Censoring times were the scheduled week of the last RNA result.

  37. Time to Confirmed Virologic Failure, Defined as First HIV-1 RNA ≥1000 Copies/mL at or After 24 Weeks on Study, With a New Resistance-associated Mutation Detected in Population-based Sequencing [CPI+SOC v SOC] [ Time Frame: From week 24 through Step 1/2 follow-up; median (IQR) step 1/2 follow-up was 72 (72,108) weeks ]
    Virologic failure was confirmed by the next HIV-1 RNA measurement ≥1000 copies/mL (irrespective of time between initial and confirmatory measure [specimens on separate dates] and treatment status). A week 24 measurement included HIV-1 RNA obtained ≥7*22=154 days after study entry (to allow for 14 day window for scheduling the visit). HIV-1 RNA measurements through and including 21 November 2016 were considered in identifying an initial failing measurement, allowing HIV-1 RNA at the close-out visit between 22 November 2016 and 13 February 2017 to be a confirmatory measure. Event times were the scheduled week of the initial failing measurement (RNA scheduled at week 0, 12, 24, 48 and every 24 weeks after). Censoring times were the scheduled week of the last RNA result. A new resistance-associated mutation is defined as one not present in the genotype prior to entry.

  38. Number of Participants With Confirmed Virologic Failure, Defined as First HIV-1 RNA ≥1000 Copies/mL at or After 24 Weeks on Study, With a New Resistance-associated Mutation Detected in Population-based Sequencing [CPI+SOC v SOC] [ Time Frame: From week 24 through Step 1/2 follow-up; median (IQR) step 1/2 follow-up was 72 (72,108) weeks ]
    Virologic failure was confirmed by the next HIV-1 RNA measurement ≥1000 copies/mL (irrespective of time between initial and confirmatory measure[specimens on separate dates] and treatment status). A week 24 measurement included HIV-1 RNA obtained ≥7*22=154 days after study entry (to allow for 14 day window for scheduling the visit).HIV-1 RNA measurements through and including 21 November 2016 were considered in identifying an initial failing measurement, allowing HIV-1 RNA at the close-out visit between 22 November 2016 and 13 February 2017 to be a confirmatory measure. A new resistance-associated mutation is defined as one not present in the genotype prior to entry.

  39. Percent of Participants With Confirmed Virologic Failure, Defined as First HIV-1 RNA ≥1000 Copies/mL at or After 24 Weeks on Study, With a New Resistance-associated Mutation Detected in Population-based Sequencing, by Week 48 [CPI+SOC v SOC] [ Time Frame: From week 24 to Week 48 ]
    Results report percent of participants reaching outcome by week 48 using Kaplan-Meier method. Virologic failure was confirmed by the next HIV-1 RNA measurement ≥1000 copies/mL (irrespective of time between initial and confirmatory measure[specimens on separate dates] and treatment status). A week 24 measurement included HIV-1 RNA obtained ≥7*22=154 days after study entry(to allow for 14 day window for scheduling the visit).HIV-1 RNA measurements through and including 21 November 2016 were considered in identifying an initial failing measurement,allowing HIV-1 RNA at the close-out visit between 22 November 2016 and 13 February 2017 to be a confirmatory measure.Event times were the scheduled week of the initial failing measurement(RNA scheduled at week 0, 12, 24, 48 and every 24 weeks after).Censoring times were the scheduled week of the last RNA result.A new resistance-associated mutation is defined as one not present in the genotype prior to entry.

  40. Time From Study Entry/Randomization to Death [CPI+SOC v SOC] [ Time Frame: From study entry through Step 1/2 follow-up; median (IQR) step 1/2 follow-up was 72 (72,108) weeks ]
    Event time was the exact week of death. Censoring time was the earlier of last contact week and the week of the last step 1/2 visit.

  41. Percent of Participants Experiencing Death by Week 48 [CPI+SOC v SOC] [ Time Frame: From study entry to Week 48 ]
    Results report percent of participants reaching outcome by week 48 using Kaplan-Meier method. Event time was the exact week of death. Censoring time was the earlier of last contact week and the week of the last step 1/2 visit.

  42. Time From Study Entry/Randomization to the First of Death, an AIDS-defining Event or a Non-AIDS-defining Event [CPI+SOC v SOC] [ Time Frame: From study entry through Step 1/2 follow-up; median (IQR) step 1/2 follow-up was 72 (72,108) weeks ]
    Event time was the exact week of death, AIDS-defining event or non-AIDS defining event. Censoring time was the earlier of last contact week and the week of the last step 1/2 visit. Only new events were considered, an event that was also reported at or prior to study entry was not included. If a participant experienced multiple events, then the time of the first event was used in the analysis. AIDS defining events included parasitic, fungal, bacterial, and viral infections as well as neoplastic diseases, and neurological disorders. Non-AIDS defining events included malignancies, diabetes, neuropathies, cardiac and renal events.

  43. Percent of Participants Experiencing Death, AIDS-defining Event or a Non-AIDS-defining Event by Week 48 [CPI+SOC v SOC] [ Time Frame: From study entry to Week 48 ]
    Results report percent of participants reaching outcome by week 48 using Kaplan-Meier method. Event time was the exact week of death, AIDS-defining event or non-AIDS defining event. Censoring time was the earlier of last contact week and the week of the last step 1/2 visit. Only new events were considered, an event that was also reported at or prior to study entry was not included. If a participant experienced multiple events, then the time of the first event was used in the analysis. AIDS defining events included parasitic, fungal, bacterial, and viral infections as well as neoplastic diseases, and neurological disorders. Non-AIDS defining events included malignancies, diabetes, neuropathies, cardiac and renal events.

  44. Time From Study Entry/Randomization to the First of Death or Hospitalization [CPI+SOC v SOC] [ Time Frame: From study entry through Step 1/2 follow-up; median (IQR) step 1/2 follow-up was 72 (72,108) weeks ]
    Event time was the exact week of death or hospitalization. Censoring time was the earlier of last contact week and the week of the last step 1/2 visit. If a participant experienced multiple events, then the time of the first event was used in the analysis.

  45. Percent of Participants With Death or Hospitalization by Week 48 [CPI+SOC v SOC] [ Time Frame: From study entry to Week 48 ]
    Results report percent of participants reaching outcome by week 48 using Kaplan-Meier method. Event time was the exact week of death or hospitalization. Censoring time was the earlier of last contact week and the week of the last step 1/2 visit. If a participant experienced multiple events, then the time of the first event was used in the analysis.

  46. Time From Study Entry/Randomization to Treatment Modification or Discontinuation [CPI+SOC v SOC] [ Time Frame: From study entry through Step 1/2 follow-up; median (IQR) step 1/2 follow-up was 72 (72,108) weeks ]
    Treatment modification is defined as the first occurrence of a substitution or subtraction of one or more drugs in the study regimen, a temporary hold lasting 7 days or longer, or the addition of a new drug to the regimen. This would not include splitting any fixed dose combination medications if the participant continues on the active drugs of the combination. Event time was the exact week of the modification or discontinuation. Censoring time was the earlier of last contact week and the week of the last step 1/2 visit.

  47. Percent of Participants With Treatment Modification or Discontinuation by Week 48 [CPI+SOC v SOC] [ Time Frame: From study entry to Week 48 ]
    Results report percent of participants reaching outcome by week 48 using Kaplan-Meier method. Treatment modification is defined as the first occurrence of a substitution or subtraction of one or more drugs in the study regimen, a temporary hold lasting 7 days or longer, or the addition of a new drug to the regimen. This would not include splitting any fixed dose combination medications if the participant continues on the active drugs of the combination. Event time was the exact week of the modification or discontinuation. Censoring time was the earliest time point between last dose week and the week of the last step 1/2 visit.

  48. Time From Study Entry/Randomization to Treatment Modification or Discontinuation Due to Toxicity [CPI+SOC v SOC] [ Time Frame: From study entry through Step 1/2 follow-up; median (IQR) step 1/2 follow-up was 72 (72,108) weeks ]
    Treatment modification is defined as the first occurrence of a substitution or subtraction of one or more drugs in the study regimen, a temporary hold lasting 7 days or longer, or the addition of a new drug to the regimen, due to an adverse event. This would not include splitting any fixed dose combination medications if the participant continues on the active drugs of the combination. Event time was the exact week of the modification or discontinuation. Censoring time was the earliest time point between last dose week and the week of the last step 1/2 visit. DAIDS AE Grading Table, Version 1.0 was used.

  49. Percent of Participants With Treatment Modification or Discontinuation Due to Toxicity by Week 48 [CPI+SOC v SOC] [ Time Frame: From study entry to Week 48 ]
    Results report percent of participants reaching outcome by week 48 using Kaplan-Meier method. Treatment modification is defined as the first occurrence of a substitution or subtraction of one or more drugs in the study regimen, a temporary hold lasting 7 days or longer, or the addition of a new drug to the regimen, due to an adverse event. This would not include splitting any fixed dose combination medications if the participant continues on the active drugs of the combination. Event time was the exact week of the modification or discontinuation. Censoring time was the earliest time point between last dose week and the week of the last step 1/2 visit. DAIDS AE Grading Table, Version 1.0 was used.

  50. Time From Study Entry/Randomization to the Development of Immune Reconstitution Inflammatory Syndrome (IRIS) [CPI+SOC v SOC] [ Time Frame: From study entry through Step 1/2 follow-up; median (IQR) step 1/2 follow-up was 72 (72,108) weeks ]
    Event time was the exact week of the diagnosis. Censoring time was the earlier of last contact week and the week of the last step 1/2 visit.

  51. Percent of Participants That Developed Immune Reconstitution Inflammatory Syndrome (IRIS) by Week 48 [CPI+SOC v SOC] [ Time Frame: From study entry to Week 48 ]
    Results report percent of participants reaching outcome by week 48 using Kaplan-Meier method. Event time was the exact week of the diagnosis. Censoring time was the earlier of last contact week and the week of the last step 1/2 visit.

  52. Time to First Dose Modification Due to Grade 3 or 4 Toxicity [CPI+SOC v SOC] [ Time Frame: From study entry through Step 1/2 follow-up; median (IQR) step 1/2 follow-up was 72 (72,108) weeks ]
    Event time was the exact week of the modification. Censoring time was the earliest time point between last dose week and the week of the last step 1/2 visit. DAIDS AE Grading Table, Version 1.0 was used.

  53. Percent of Participants With a Dose Modification Due to Grade 3 or 4 Toxicity by Week 48 [CPI+SOC v SOC] [ Time Frame: From study entry to Week 48 ]
    Results report percent of participants reaching outcome by week 48 using Kaplan-Meier method. Event time was the exact week of the modification. Censoring time was the earliest time point between last dose week and the week of the last step 1/2 visit. DAIDS AE Grading Table, Version 1.0 was used.

  54. Change From Baseline in CD4+ T-cell Count [CPI+SOC v SOC] [ Time Frame: Baseline, week 24, 48, and 72 ]
    Baseline is defined as the last measurement obtained on or before the earlier of the following two dates: the date of entry/randomization plus three days (this is the time allowed in the protocol for starting study-defined ART) and the date of starting the study-defined ARV regimen.

  55. Change From Baseline in Fasting Values of Total Cholesterol [CPI+SOC v SOC] [ Time Frame: Baseline, week 24, 48, and 72 ]
    Baseline is defined as the last measurement obtained on or before the earlier of the following two dates: the date of entry/randomization plus three days (this is the time allowed in the protocol for starting study-defined ART) and the date of starting the study-defined ARV regimen.

  56. Change From Baseline in Fasting Values of High-density Lipoprotein Cholesterol [CPI+SOC v SOC] [ Time Frame: Baseline, week 24, 48, and 72 ]
    Baseline is defined as the last measurement obtained on or before the earlier of the following two dates: the date of entry/randomization plus three days (this is the time allowed in the protocol for starting study-defined ART) and the date of starting the study-defined ARV regimen.

  57. Change From Baseline in Fasting Values of Calculated Low-density Lipoprotein Cholesterol [CPI+SOC v SOC] [ Time Frame: Baseline, week 24, 48, and 72 ]
    Baseline is defined as the last measurement obtained on or before the earlier of the following two dates: the date of entry/randomization plus three days (this is the time allowed in the protocol for starting study-defined ART) and the date of starting the study-defined ARV regimen.

  58. Change From Baseline in Fasting Values of Triglycerides [CPI+SOC v SOC] [ Time Frame: Baseline, week 24, 48, and 72 ]
    Baseline is defined as the last measurement obtained on or before the earlier of the following two dates: the date of entry/randomization plus three days (this is the time allowed in the protocol for starting study-defined ART) and the date of starting the study-defined ARV regimen.

  59. Change From Baseline in Fasting Values of Glucose [CPI+SOC v SOC] [ Time Frame: Baseline, week 24, 48, and 72 ]
    Baseline is defined as the last measurement obtained on or before the earlier of the following two dates: the date of entry/randomization plus three days (this is the time allowed in the protocol for starting study-defined ART) and the date of starting the study-defined ARV regimen.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria for Step 1:

  • HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA VL.
  • Any previous combination of ARV treatment at any time with at least one regimen that contained one NNRTI and two NRTIs which was replaced with a PI-based regimen because of virologic, immunologic, or clinical treatment failure, or because of toxicity.

NOTE: All potential participants with prior RAL exposure were assigned to either Cohort A or Cohort D.

  • At screening, receipt of a PI-based regimen with no regimen change for a minimum of 24 weeks prior to screening.
  • Confirmation of VF of current second-line PI-based ART. NOTE A: Failure of the current second-line regimen was defined as two consecutive measurements of plasma HIV-1 RNA ≥1000 copies/mL obtained at least 1 day apart while on the current PI-based regimen. "Current PI-based regimen" and "current regimen" were understood to be the regimen described (ie, the regimen that the candidate was taking when the first VF sample was drawn plus only those modifications allowed).
  • CD4+ T-cell count result from a specimen drawn within 103 days prior to study entry
  • Laboratory values obtained within 30 days prior to study entry:

    • Absolute neutrophil count (ANC) ≥ 500/mm^3
    • Hemoglobin ≥7.5 g/dL
    • Platelet count ≥40,000/mm^3
    • Creatinine ≤2 X upper limit of normal (ULN)
    • Aspartate aminotransferase (AST), serum glutamic oxaloacetic transaminase (SGOT), alanine aminotransferase (ALT), serum glutamic pyruvic transaminase (SGPT), and alkaline phosphatase ≤5 x ULN
    • Total bilirubin ≤2.5 x ULN
    • Creatinine clearance (CrCl) >30 mL/min, either measured or estimated by Cockcroft-Gault equation
    • Hepatitis B panel that includes HbsAB, HBcAB, and HBsAG or only HBsAG, with plasma stored for later anti-HBs and anti-HBc.

NOTE A: Candidates who were eligible for cohort B and who were positive for active hepatitis B infection were assigned to sub-cohort B3 at registration/randomization.

NOTE B: Candidates with CrCl <60 mL/min who were also positive for active hepatitis B infection were not eligible.

  • Females of reproductive potential (women who have not been post-menopausal for at least 24 consecutive months, ie, who have had menses within the preceding 24 months, or women who have not undergone surgical sterilization, hysterectomy or bilateral salpingectomy or bilateral oophorectomy or tubal ligation) must have had a negative serum or urine pregnancy test prior to the submission of the screening genotype testing sample and again within 48 hours prior to randomization or registration.
  • Female participants of reproductive potential must have agreed not to participate in the conception process (ie, active attempt to become pregnant, in vitro fertilization), and if participating in sexual activity that could lead to pregnancy, the female participant must have used at least one reliable form of contraceptive. Female participants must have continued to use contraceptives while receiving study treatment and for 6 weeks after stopping study treatment.

Acceptable forms of contraceptives included:

  • Condoms (male or female) with or without a spermicidal agent
  • Diaphragm or cervical cap with spermicide
  • Intrauterine device (IUD)
  • Hormonal contraception

Female participants who were not of reproductive potential or whose male partner(s) had documented azoospermia) were not required to use contraceptives. Any statement of self-reported sterility or that of her partner's must have been entered in the source documents.

NOTE: Acceptable documentation of lack of reproductive potential was oral or written documentation from the participant.

  • Karnofsky performance score >/= 70 within 30 days prior to study entry.
  • Ability and willingness of potential participant to provide informed consent.
  • Willingness of potential participant to adhere to protocol requirements, especially with respect to treatment assignment and ability to obtain non-study provided ART, if needed.
  • Ability to take oral study medications.
  • No intention of permanent relocation that would preclude attending Step 1 and 2 study follow-up visits.
  • Availability of a successful, interpretable resistance genotype report from a DAIDS-approved regional genotyping facility from testing performed on a plasma sample that was collected during screening (ie, at or after the date that a sample is collected to confirm HIV-1 virologic failure) and which was shipped to a regional resistance testing laboratory once documentation of two screening plasma HIV-1 RNA values ≥1000 copies/mL were available.
  • Identification of a cohort assignment and ARV regimen for use on study, selected from the recommended options provided by the site investigator, and reviewed and approved by the A5288 Clinical Management Committee (CMC).

Exclusion Criteria for Step 1:

  • Pregnancy or breast-feeding.
  • Known allergy/sensitivity or any hypersensitivity to components of study drugs or their formulation.
  • Active drug or alcohol use or dependence that, in the opinion of the site investigator, would have interfered with adherence to study requirements.
  • Serious illness requiring systemic treatment and/or hospitalization until candidate either completes therapy or was clinically stable on therapy, in the opinion of the site investigator, for at least 7 days prior to study entry.
  • Concurrent illness or condition that would compromise the ability to take study medication, follow the protocol, or that would make participation not in the best interest of the participant, per the site investigator.
  • Requirement for taking any of the prohibited medications with the selected ARV study regimen, or within 14 days prior to study entry.

NOTE: Study candidates should not have discontinued any component of their ART during screening. The 14-day restriction on prohibited medications did not apply to ARVs.

  • Active tuberculosis (TB) or rifampin exposure less than 2 weeks prior to study entry.
  • Any exposure to darunavir or etravirine.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01641367


Locations
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Brazil
Hospital Nossa Senhora da Conceicao CRS (12201)
Porto Alegre, RS, Brazil, 9043010
Instituto de Pesquisa Clinica Evandro Chagas (12101)
Rio de Janeiro, Brazil, 21045
Haiti
Les Centres GHESKIO CRS (30022)
Port-au-Prince, Bicentaire, Haiti, HT-6110
GHESKIO Institute of Infectious Diseases and Reproductive Health (GHESKIO - IMIS) CRS
Port Au Prince, Haiti
India
BJ Medical College CRS (31441)
Pune, Maharashtra, India, 411001
Chennai Antiviral Research and Treatment (CART) CRS (11701)
Chennai, Taramani, India, 600113
Kenya
AMPATH at Moi Univ. Teaching Hosp. Eldoret CRS (12601)
Eldoret, Kenya, 30100
Kenya Medical Research Institute/Center for Disease Control (KEMRI/CDC) CRS (31460)
Kisumu, Kenya, 40100
Malawi
Malawi CRS (12001)
Lilongwe, Malawi
Peru
San Miguel CRS (11302)
San Miguel, Lima, Peru
Barranco CRS (11301)
Lima, Peru, 18 PE
South Africa
University of the Witwatersrand Helen Joseph (WITS HJH) CRS (11101)
Johannesburg, Gauteng, South Africa, 2193
Family Clinical Research Unit (FAM-CUR) CRS (8950)
Cape Town, West Cape, South Africa, 7505
Durban Adult HIV CRS (11201)
Durban, South Africa, 4013 SF
Soweto ACTG CRS (12301)
Johannesburg, South Africa
Thailand
31802 Thai Red Cross AIDS Research Centre (TRC-ARC) CRS
Bangkok, Patumwan, Thailand, 10330
31784 Chiang Mai University HIV Treatment CRS
Chiang Mai, Thailand, 50200
Uganda
JCRC CRS
Kampala, Uganda
Zimbabwe
UZ-Parirenyatwa CRS (30313)
Harare, Zimbabwe
Sponsors and Collaborators
AIDS Clinical Trials Group
National Institute of Allergy and Infectious Diseases (NIAID)
AbbVie
Gilead Sciences
Janssen Pharmaceuticals
Merck Sharp & Dohme Corp.
Dimagi Inc.
Investigators
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Study Chair: Beatriz Grinsztejn, MD, PhD Instituto de Pesquisa Clinica Evandro Chagas-Fiocruz
Study Chair: Peter Mugyenyi, MB ChB, FRCP, DSc Joint Clinical Research Center

Additional Information:
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Responsible Party: AIDS Clinical Trials Group
ClinicalTrials.gov Identifier: NCT01641367     History of Changes
Other Study ID Numbers: ACTG A5288
1U01AI068636 ( U.S. NIH Grant/Contract )
First Posted: July 16, 2012    Key Record Dates
Results First Posted: February 20, 2018
Last Update Posted: March 15, 2019
Last Verified: March 2019

Additional relevant MeSH terms:
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Tenofovir
Raltegravir Potassium
Emtricitabine
Darunavir
Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
Etravirine
HIV Protease Inhibitors
Protease Inhibitors
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents
HIV Integrase Inhibitors
Integrase Inhibitors